Original Articles
Induced sputum and bronchoalveolar lavage as tools for evaluating the effects of inhaled corticosteroids in patients with asthma,☆☆

https://doi.org/10.1067/mlc.2000.107305Get rights and content

Abstract

Changes in airway inflammation can be studied with bronchoalveolar lavage, but the widespread use of this procedure is limited by its invasiveness. The aim of this study was to evaluate the usefulness of induced sputum as a non-invasive alternative to bronchoalveolar lavage for studying changes in airway inflammation in patients with asthma. Thirty patients were treated for 12 weeks with an inhaled corticosteroid (fluticasone propionate [FP], 250 μg twice daily) or a short-acting beta-agonist (salbutamol [Sb], 400 μg twice daily) in a double-blind, double-dummy, randomized parallel group study. Sputum induction with hypertonic saline solution was performed twice before treatment and after 4, 8, 10, and 11 weeks of treatment. Bronchoalveolar lavage fluid divided into two pools (first 60 mL portion as bronchoalveolar lavage/bronchial wash [BAL/BW] and subsequent 80 mL as bronchoalveoalar lavage [BAL]) was obtained before and after 12 weeks of treatment. Changes in cell differentials and plasma-protein leakage (α2-macroglobulin, albumin, and their ratio [relative coefficient of excretion, RCE]) were analyzed in induced sputum and were compared with changes in BAL/BW and BAL. During treatment with FP, the PC20histamine (interpolated concentration of histamine that caused a fall in FEV1 of 20% of the baseline value) increased (P <.0001), and the percentage of eosinophils (P =.004), levels of α2-macroglobulin (P =.09) and RCE (P =.007) decreased in sputum. These changes were different from those in the Sb group (PC20histamine P <.0001, eosinophils P =.004, α2-macroglobulin P =.003, RCE P =.01), in which α2-macroglobulin showed a significant increase (P =.015). Changes in the percentage of eosinophils and in the levels of α2-macroglobulin in sputum were associated with changes in the PC20histamine (Rs = –0.59, P =.007 and Rs = –0.47, P =.03, respectively). These correlations did not reach significance in BAL/BW and BAL fluid. The statistical power to detect changes in induced sputum was higher for the percentage of eosinophils and similar for plasma protein leakage as compared with analysis of BAL/BW and BAL fluid. We conclude that the analysis of induced sputum is a useful, non-invasive alternative to bronchoalveolar lavage for assessing the effects of antiinflammatory drugs in asthma. (J Lab Clin Med 2000;136:39-49)

Section snippets

Patients

Patients were included as reported earlier11 according to the criteria summarized below. Thirty-three patients with mild to moderate asthma, 19 men and 14 women, were recruited for this study from our institution's outpatient clinic of pulmonology. Asthma was diagnosed according to the American Thoracic Society criteria and included a history of recurrent episodes of wheezing, chest tightness, and dyspnea and normal lung function between asthmatic attacks.12 Asthma severity before the

Results

Thirty-three patients agreed to participate in the study. Three did not fulfill the inclusion criteria during the run-in period. Two of them had a persistent FEV1 of less than 60% of predicted, and the other had an exacerbation of asthma symptoms requiring additional medication. Thirty patients were randomized to receive FP (n = 15) or Sb (n = 15). At the time of entry into the treatment period, no significant differences were observed in baseline characteristics between the two treatment

Discussion

The patients receiving inhaled corticosteroids improved clinically from 4 weeks onward, with a significant increase in histamine threshold after 12 weeks of treatment (mean, 2.4 doubling doses).11 Here we demonstrate that in sputum from these patients, the percentage of eosinophils—and to a lesser extent also the parameters for plasma protein leakage—significantly decreased from 4 weeks onward. In the patients receiving Sb there was an increase in nonspecific bronchial hyperreactivity and an

Acknowledgements

We want thank R. Lutter for reading the manuscript carefully and R. de Haan for advice on statistical methods.

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      Another caveat to our study is that some investigators use a different method of SI in which mucus conglomerations were separated from induced sputum, homogenized, and then used for the assessment of inflammation (eg, with cell counts and determination of biochemical parameters). We used the homogenized, whole induced sputum method that was recommended by the Asthma Clinical Research Network2 and used by Fahy et al,56 Hiltermann et al,29 and Nocker et al9 in the studies discussed above. It is unclear whether our results using the method recommended by the Asthma Clinical Research Network can be extrapolated to the mucus conglomeration method.

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    Supported by a grant from GlaxoWellcome (R.E.T.N.).

    ☆☆

    Reprint requests: J. S. van der Zee, MD, Academic Medical Center, Department of Pulmonology, F4-208, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.

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